Pharmaceutical drugs that are manufactured, extracted, or synthesized from biological sources are required to go through virus reduction steps to mitigate the potential of viral contamination in the drug product. Similarly, blood products and derivatives are required to go through virus reduction steps to mitigate the potential of viral contamination in the product. One such known method of virus reduction is through size exclusion filtering. Through size exclusion filtering, a feed flow containing the product to be filtered is passed through a virus removal filter. The virus removal filter has a virus filtration membrane that traps viruses to be removed from the product. To trap the virus, the membrane is manufactured to have millions of voids that connect to multiple capillaries that interconnect to form a lattice the fluid must pass through to exit the filter. Therefore, a virus entrained in the fluid flow has a torturous path to find a way through the virus filter membrane to exit. On this torturous path, a virus may get trapped in or about a capillary by size exclusion. It may also be held up in a void by fluid forces or affinity to the void wall. Thus, for example, to trap a virus having a 17 nanometers (“nm”) cross-sectional diameter, the capillaries must have a cross section diameter of less than 17 nm somewhere along their length or a void must retain a virus having less than a 17 nanometer cross-sectional diameter by fluid forces or affinity to the walls of the void.
A reduction in feed flow through the virus removal filter may occur for various reasons during the filtration process. For example, a reduction in feed flow through the virus removal filter may occur as a result of a reduction in supply to the filter. Alternatively or additionally, a reduction in feed flow through the virus removal filter may occur as a result of valve switching, fitting failure, pneumatic failure, mechanical failure, electrical failure, and other intentional or non-intentional acts or events. In any case, as a result of such a reduction in feed flow, flow through the virus removal filter will become reduced or even discontinuous.
However, a virus which is retained by fluid flow or affinity to the walls of a void may find its way out of retention by Brownian motion when fluid flow through the void is reduced (either partially or completely). In other words, during reduced feed flow, a virus may move about a void by Brownian motion. Brownian motion may move a virus far enough away from where it was retained in the void that when full feed flow resumes through the void, a virus gets entrained in the flow and exits the void into a capillary or another void. When a virus gets entrained in the flow and exits a void after once being retained by that void, it has another chance to migrate through the virus filtration membrane, thereby undesirably increasing the chances that the virus will pass completely through the virus removal filter.
Thus, reduced or discontinuous feed flow through a virus removal filter, during the filtration process, will result in a higher probability of a virus migrating through the virus removal filter when full feed flow resumes. In other words, reduction in feed flow through a virus removal filter, during the filtration process, will increase the probability of a virus making its way through the virus removal filter when full feed flow resumes. It will therefore be appreciated that the reduction of feed flow through a virus removal filter, during the filtration process, is a concern.